1. Field of the Invention
The present invention relates to a gene delivery system containing nanoparticles.
2. Description of the Related Art
Gene therapy is attractive as a clinical treatment for cancers and genetic disorders of both congenital and acquired origins [1]. Efficient gene delivery systems are central to the clinical treatment of genetic disorders and cancer and have attracted considerable attention in recent years [1]. The use of recombinant viruses as gene carriers was the focus of early studies due its high transfection efficiencies and levels of protein expressions [2]. However, these systems are critically limited because viral proteins trigger strong immune responses, which has resulted in a lack of FDA-approved products [3]. Additionally, viral delivery systems are limited in scale-up procedures [4]. As a result, numerous nonviral gene delivery systems such as cationic lipids, polymers, dendrimers, and peptides have been developed [5]. However, unlike, nonviral gene delivery systems exhibit significantly reduced transfection efficiencies compared to viral systems due to numerous extra- and intracellular obstacles. Therefore, many researchers continue to focus on designing safe and efficient viral delivery vectors.
Recently, nanomaterials, including carbon nanotubes and iron oxide, silica, and gold nanoparticles, have been intensively studied as alternative nonviral gene delivery systems [6]. Gold nanoparticles are attractive scaffolds for the creation of gene delivery systems because they are bioinert, nontoxic, and easily synthesized and functionalized [7]. Thus far, several strategies for gene delivery systems have been developed, including mixed monolayer protected gold nanoparticles, complexes of polymer and gold nanoparticles, double-stranded DNA functionalized gold nanoparticles, and single stranded DNA functionalized gold nanoparticles [8]. Single-stranded DNA functionalized gold nanoparticles developed by Mirkin et al. were a good gene delivery system and antisense [8f]. Moreover, these nanoparticles showed greater knockdown of gene expression, higher binding affinity for target DNA, higher immunity to nuclease, and lower cell toxicity than antisense DNA delivered by either Lipofectamine or Cytofectin.
However, the system could deliver only antisense DNA covalently cross-linked to gold nanoparticles, which needed to be individually synthesized for each gene of interest, procedures that are both time consuming and inconvenient.
Therefore, there has been demanded for a gene delivery system that can be used for delivery of any antisense DNA oligo without a need for the synthesis of the gold nanoparticles covalently linked to antisense DNA oligo specific to the gene of interest.
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.